HELMINTH & THEIR CUTANEOUS MANIFESTATIONS

Brittany Grady, DO DISCLOSURES

I have no conflicts of interest to declare LEARNING OBJECTIVES:

• Describe the cutaneous manifestations of helminth infections

• Recognize recent developments and incidence of helminth infections within the of America

• Evaluate, diagnose, and treat affected patients more knowledgeably and effectively WHAT IS A HELMINTH?

• Helminths () are large, multicellular organisms

• Often visible to the naked eye

• Free-living or parasitic

• Belong to 2 different phyla:

• Roundworms ()

• (Platyhelminthes) ROUNDWORMS (NEMATODES)

• Unsegmented

• Each species has 2 different sexes

• Contain a body cavity and digestive tract FLATWORMS (PLATYHELMINTHES)

• Segmented or unsegmented • Primarily hermaphroditic • Do not have a body cavity • Further subdivided into 2 different classes: • Flukes (Trematodes) • Tapeworms (Cestodes) ROUNDWORM () INFECTIONS

• Cutaneous Migrans

•

•

•

•

• (CLM)

• AKA Creeping Eruption

• CLM primarily affects people in tropical and subtropical climates, including the SE United States

• Caused by , most commonly and A. caninum

• are eliminated via animal (cat or ) feces and larvae mature in the sand/soil

• Larvae infiltrate exposed surfaces of humans (end hosts)

• Confined to the (lack collagenase) CLM

X X X CUTANEOUS LARVA MIGRANS (CLM)

• Larval migration through the epidermis (1-2 cm/day)

• Clinical features:

• Localized, intense pruritus

• Linear or serpiginous raised erythematous “tracts”

• +/- vesiculation

• Most frequent location is distal lower extremities or buttocks

• Diagnosis usually made clinically ( rarely helpful) W. Infectious of the Skin. In: McKee’s Pathology of the Skin 4th ed. Edinburgh: ElsevierGrayson/Saunders; 2012: 761-895 Nelson SA, Warschaw KE. and Worms. In: Dermatology 3rd ed. Edinburgh: Elsevier/Saunders; 2012: 1391-1421 www.visualdx.com Grady BE, Baum B. A Classic Case of Cutaneous Larva Migrans. 2013. http://www.consultantlive.com/skin-diseases/content/article/10162/2148906 CUTANEOUS LARVA MIGRANS (CLM)

• Self-limited, but patients typically seek medical treatment

• Treatment options:

• PO 400-800mg/day (Peds: 10-15 mg/kg/day) x 3-5 days

• PO 12mg (Peds: 150 mcg/kg) x 1

• Topical 10-15% thiabendazole solution or ointment TID x 15 days

• Cryotherapy to leading edge of skin tract (often unreliable) ONCHOCERCIASIS

• AKA River Blindness

• Onchocerciasis primarily affects people in tropical

• Caused by volvulus

• Transmitted via blood meal of infected black ( spp.)

• Larvae mature into adult worms in the dermis and subcutis

• Mature adult female worms become encapsulated in fibrous tissue (onchocercomas)

• Each produces hundreds of microfilariae which migrate to the skin, connective tissue, eyes, and lymph nodes Grayson W. Infectious Diseases of the Skin. In: McKee’s Pathology of the Skin 4th ed. Edinburgh: Elsevier/Saunders; 2012: 761-895 Grayson W. Infectious Diseases of the Skin. In: McKee’s Pathology of the Skin 4th ed. Edinburgh: Elsevier/Saunders; 2012: 761-895 www.who.int/intestinal_worms/en ONCHOCERCIASIS

• Clinical features:

• Onchocercomas- firm, freely mobile subQ nodules often located over bony prominences

• Acute papular onchodermatitis chronic onchodermatitis lichenification, , depigmentation

• “Hanging groin”- chronic lymphatic obstruction of inguinal lymph nodes

• Progressive sclerosing can lead to blindness in severe cases

• 2nd most common cause of -related blindness

• Accounts for 0.8% of overall blindness globally www.visualdx.com Nelson SA, Warschaw KE. Protozoa and Worms. In: Dermatology 3rd ed. Edinburgh: Elsevier/Saunders; 2012: 1391-1421 www.visualdx.com Grayson W. Infectious Diseases of the Skin. In: McKee’s Pathology of Nelson SA, Warschaw KE. Protozoa and Worms. In: Dermatology the Skin 4th ed. Edinburgh: Elsevier/Saunders; 2012: 761-895 3rd ed. Edinburgh: Elsevier/Saunders; 2012: 1391-1421 Grayson W. Infectious Diseases of the Skin. In: McKee’s Pathology of the Skin 4th ed. Edinburgh: Elsevier/Saunders; 2012: 761-895 ONCHOCERCIASIS

• Treatment options:

• DOC: PO Ivermectin 150 mcg/kg x 1 q3-12 months

• Treatment continued for worm’s lifetime (10-15 years)

• Adjunct: PO 100-200mg/day x 6 weeks

• Targets endobacteria that reside within the O. volvulus nematodes

• Wolbachia is responsible for that leads to subsequent protective

• Nodulectomy: surgical removal of onchocercomas from head/neck reduces the incidence of ocular

FILARIASIS

• AKA

• Filariasis primarily affects individuals in tropical or subtropical regions, including the Caribbean Islands and

• Caused by Wucheria bancrofti (90% of cases)

• Transmitted via bite of infected mosquitoes

• Deposited larvae migrate to and develop into adult worms

• Adult worms release microfilariae into the bloodstream Cano J, Rebollo MP, Golding N, et al. The Global Distribution and Limits of : Past and Present. Parasites & Vectors. 2014 Oct; 7: 466 www.visualdx.com FILARIASIS

• After 10-15 years of infection, the clinical features of chronic disease become evident

• Leading cause of permanent disability worldwide

• Clinical features:

• Acute adenolymphangitis associated with and chills (recurrent)

• Chronic  hypertrophy of skin (hyperkeratotic, verrucous, fibrotic) redundant folds deformity

• Secondary bacterial and fungal infections common

• Most commonly affected sites: lower extremities and genitalia www.visualdx.com www.visualdx.com James WD, Berger TG, Elston DM. Parasitic , Stings, and Bites. In: Andrews’ Diseases of the Skin: Clinical Dermatology 11th ed. Edinburgh: Elsevier/Saunders; 2011: 414-447 FILARIASIS

• Treatment options:

• DOC: PO 6 mg/kg/day x 12 days

• Active against microfilariae, limited effect on adult worms

• Adult worm lifespan in approx. 5-10 years

• Adjunct: PO Doxycycline 200mg/day x 4-8 weeks

• Targets Wolbachia endobacteria

• Supportive care: limb elevation, compression stockings, protection from trauma, NSAIDs

STRONGLYLOIDIASIS

• AKA Larva Currens • Worldwide distribution, especially in tropical and subtropical regions, including SE United States and Appalachia • Caused by the Strongyloides stercoralis • Transmitted via direct contact with free-living larvae, usually through contaminated soil • Larvae penetrate skin  migrate to intestine to mature into adult worms  lay eggs  develop into infective larvae in intestine • Infective larvae migrate toward the perianal opening • Penetrate skin

Puthiyakunnon S, Boddu S, Li Y, et al. Strongyloidiasis-An Insight into Its Global Prevalence and Management. PLoS Negl Trop Dis. 2014 Aug; 8(8): e3018 www.cdc.gov/par asites STRONGLYLOIDIASIS

• Most patients with strongyloidiasis are asymptomatic

• Larval migration through skin (up to 10 cm/day)

• Clinical features:

• Urticarial serpiginous, raised, erythematous “tract” usually located on the buttocks or trunk

• Autoinfection can cause the to recur for weeks to years

• Hyperinfection with Strongyloides- diffuse petechiael “thumbprint purpura” eruption

• Seen in immunocompromised individuals

• Dermal invasion of a large number of larvae that migrate through vessel walls

• High mortality www.cdc.gov/parasi tes www.visualdx.com STRONGLYLOIDIASIS

• Recommended to treat all known infected patients, whether symptomatic or not

• Consider testing patients at risk prior to initiating immunosuppressive drugs i.e.

• Microscopic stool examination

• Treatment options:

• DOC: PO Ivermectin 0.2 mg/kg/day x 2 days (consider repeating in 2 weeks)

• PO Albendazole 400 mg BID x 7 days

• PO Thiabendazole 25 mg/kg BID x 2 days (7-10 days for hyperinfection syndrome) TRICHINOSIS

• Worldwide distribution, including the United States

• Caused by Trichinella spp. (most commonly )

• Transmission via ingestion of larva-containing in raw or undercooked meat

• Ingested larvae invade small bowel and mature into adult worms

• Adult female worms release larvae that migrate to striated muscle and encyst (may remain viable for several years)

• Disease severity categorized as light (1-10 ingested larvae), moderate (50-500 ingested larvae), or severe (>1000 ingested larvae) www.visualdx.com TRICHINOSIS

• are the most common source of human infection

• Typically from consumption of home-prepared sausage or undercooked wild game in the U.S.

• Worldwide incidence has declined dramatically in past 2-3 decades

• Improved -raising practices

• Improved inspection processes

• Commercial and home freezing of

• Public awareness of danger of eating undercooked meats www.cdc.gov/para sites www.cdc.gov/parasites TRICHINOSIS

• Nonspecific GI symptoms occur first (1-2 days post consumption) • Classic symptoms occur within 2 weeks of eating contaminated meat • Clinical features: • Myalgias (approx. 90% cases) • Periorbital • Nonpruritic morbilliform exanthem (uncommon) • Subungual splinter hemorrhages • Rare, severe cases may affect CNS, , and/or  death www.visualdx.com www.visualdx.com TRICHINOSIS

• Self-limited if mild disease

• Treatment options:

• PO Corticosteroids- Prednisone 40-60 mg/day until symptoms resolve (followed by gradual taper)

• Highly recommended to address allergic-reaction related

• Especially if CNS, cardiac, or pulmonary involvement

• Caution: monotherapy may decrease the number of adult worms expelled via GI tract increased number of larvae produced

• PO Albendazole 400 mg BID x 8-14 days

• PO 200-400 mg TID x 3 days, then 400-500 mg TID x 10 days TOXOCARIASIS

• Endemic in the United States

• Highest prevalence in hot, humid regions

• Caused by and T. catis (dog and cat roundworms, respectively)

• Transmission via accidental ingestion of eggs from the environment or (more rarely) ingestion of undercooked meat infected with Toxocara larvae

• Eggs hatch and travel hematogenously to various body tissues including , heart, , lungs, muscles, or eyes

• Disease primarily affects children

• 13.9% of the U.S. population ≥ 6 years of age are seropositive for toxocariasis TOXOCARIASIS

• A U.S. study in 1996 showed that 30% of younger than 6 months deposit Toxocara eggs in their feces

• Studies have shown that almost all puppies are born already infected with Toxocara canis

• Research suggests that 25% of all cats are infected with

• Via Centers for Disease Control and Prevention (CDC) TOXOCARIASIS

• Most people who are infected do not have any symptoms

• Manifestations reflect the number of migrating larvae, where the larvae have migrated in the body, and the degree of inflammation that developed in response to the presence of the larvae

• Clinical features:

• Transient rash, chronic urticaria, eczematous dermatitis, cutaneous nodules

• In 2 case control studies, 65% of patients with chronic urticaria and 38.1% of patients with chronic prurigo were found to be seropositive for Toxocara

• Anti-helminthic treatment cured the chronic urticaria in 50% of cases and the chronic prurigo in 80% of cases

• Visceral toxocariasis

• Ocular toxocariasis- at least 70 people are blinded by this disease each year in the U.S. www.cdc.gov/mmwr/preview/mmwrhtml/mm6022a2.htm Kollipara R, Peranteau AJ, Nawas ZY, et al. Emerging Infectious Diseases with Cutaneous Manifestations. J Am Acad Dermatol. 2016 Jul; 75(1): 19-31 TOXOCARIASIS

• Treatment indicated for symptomatic visceral or ocular disease

• Treatment options:

• PO Albendazole 400 mg BID x 5 days

• PO Mebendazole 100-200 mg BID x 5 days

• Systemic corticosteroids may be necessary to control inflammatory response (PLATYHELMINTH) INFECTIONS

• Fluke (Trematode) infections

•

• Tapeworm (Cestode) infections

• SCHISTOSOMIASIS

• AKA Bilharziasis, Cercarial Dermatitis, “Swimmer’s ”

• Worldwide distribution, especially tropical climates

• Caused by mansoni, S. haematobium, and S. japonicum (human schistosomes- not seen in U.S.)

• Caused by Trichobilharzia and Bilharziella spp. (avian schistosomes- seen in Northern U.S. and California)

• Transmission via direct contact with free-living larvae released by freshwater snails SCHISTOSOMIASIS (HUMAN)

• Larvae penetrate skin within minutes of contact  dermis  vascular system

• Larvae mature into adult worms within vascular system (mesenteric )

• Adults deposit eggs in venules  intestines (S. mansoni, S. japonicum) or bladder (S. haematobium)

• Eggs eliminated via feces or urine SCHISTOSOMIASIS (AVIAN)

• Larvae penetrate skin within minutes of contact

• Remain in stratum corneum

• Humans are accidental “dead end” hosts

• Larvae die shortly (within hours) after initial penetration Grayson W. Infectious Diseases of the Skin. In: McKee’s Pathology of the Skin 4th ed. Edinburgh: Elsevier/Saunders; 2012: 761-895 www.cdc.gov/parasites www.cdc.gov/parasites SCHISTOSOMIASIS

• Skin manifestations begin within minutes to hours

• Represent a hypersensitivity reaction to larval penetration of skin

• Clinical features:

• Cercarial dermatitis “swimmer’s itch”- urticarial, pruritic erythematous papular eruption

• Most commonly on lower legs/feet

• Seen with both human and avian schistosome larvae

• Katayama - fever, chills, , headache

• Hypersensitivity reaction against migrating human schistosome larvae

• Bilharziasis cutanea tarda- papular, granulomatous, or verrucous lesions

• Seen in those with chronic, visceral disease

• Secondary to deposition of eggs in the dermis

• Genital and perineal regions most commonly affected James WD, Berger TG, Elston DM. Parasitic Infestations, Stings, and Nelson SA, Warschaw KE. Protozoa and Worms. In: Dermatology 3rd ed. Edinburgh: Bites. In: Andrews’ Diseases of the Skin: Clinical Dermatology 11th Elsevier/Saunders; 2012: 1391-1421 ed. Edinburgh: Elsevier/Saunders; 2011: 414-447 Grayson W. Infectious Diseases of the Skin. In: McKee’s Pathology of the Skin 4th ed. Edinburgh: Elsevier/Saunders; 2012: 761-895 SCHISTOSOMIASIS

• Cercarial dermatitis (acute skin eruption) is self-limiting, but may persist for several weeks

• Treatment options (human):

• DOC: PO 20 mg/kg BID-TID x 1

• Treatment options (avaian):

• No treatment required for cercarial dermatitis caused by avian schistosomes

• Antihistamines and topical corticosteroids for symptomatic relief CYSTICERCOSIS

• Worldwide distribution, including the United States (most commonly SW U.S.)

• Caused by solium (pork tapeworm)

• Transmission via fecal-oral ingestion of eggs via contaminated food or water

• Ingested eggs hatch in the small bowel and penetrate intestinal mucosa

• Spread hematogenously and encyst in various body tissues including muscle, brain (), heart, eyes, and skin

• Cysts remain viable for 3-5 years CYSTICERCOSIS

• Cysticercosis versus • You cannot acquire cysticercosis from ingestion of infected undercooked pork • A quick word about Taeniasis… • Ingestion of T. solium larval cysts in undercooked pork • Leads to of small bowel with adult tapeworms (compared to eggs ingested in cysticercosis) • Tapeworm lives and grows (up to 30 feet!) within the intestine • Gravid proglottids or eggs are shed and expelled via feces (individual now an infectious carrier of disease) • Autoinfection not uncommon  ingestion of eggs  cysticercosis www.cdc.gov/parasites www.cdc.gov/p arasites CYSTICERCOSIS

• Incidence is rising in the United States, especially in states with a large immigrant population (most commonly from endemic )

• Cases are most frequently reported in New York, California, Texas, Oregon, and Illinois

• There are an estimated 1,000 new hospitalizations for neurocysticercosis in the United States each year

• Neurocysticercosis is a leading cause of adult onset worldwide

Sorvillo, FJ, DeGiorgio C, Waterman SH. Deaths from Cysticercosis, United States. Emerg Infect Dis. 2007 Feb; 13(2): 230-235 CYSTICERCOSIS

• Clinical features:

• Multiple, asymptomatic, firm subQ or intramuscular 1-2 cm nodules

• Can resemble other common cutaneous lesions such as lipomas or epidermoid cysts

• Muscle involvement often associated with myalgias and fever

• Neurocysticercosis can present with

• Intraocular cysticercosis may lead to vision loss Grayson W. Infectious Diseases of the Skin. In: McKee’s Pathology of the Skin 4th ed. Edinburgh: Elsevier/Saunders; 2012: 761-895 Kollipara R, Peranteau AJ, Nawas ZY, et al. Emerging Infectious Diseases with Cutaneous Manifestations. J Am Acad Dermatol. 2016 Jul; 75(1): 19-31

CYSTICERCOSIS

• The natural history of the lesions of cysticercosis is spontaneous resolution (cysts degenerate after 3-5 years) • Studies have indicated that treated patients with neurocysticercosis have fewer residual seizures than those not treated with an anti-helminthic • Inactive lesions of cutaneous cysticercosis are treated surgically • Treatment options: • DOC: PO Albendazole 15 mg/kg/day x at least 8 days • PO Praziquantel 50 mg/kg/day (in 3 divided doses) x 14 days • Consider systemic corticosteroids prior to initiation of anti- helminthic therapy FINAL THOUGHTS

• 21st century has brought increased international travel for vacation, business, medical missions, and immigration Via U.S. Dept. of State Via U.S. Dept. of Commerce Via U.S. Dept. of Commerce FINAL THOUGHTS

• Approx. 17% of travelers seek medical care because of cutaneous disorders

• Helminth infections are important causes of morbidity and mortality worldwide

• Although many helminth infections are uncommon in the United States, it is important to be aware of these conditions (they do exist!)

• Little research has been done to calculate the burden of these diseases within the United States

REFERENCES

• Cano J, Rebollo MP, Golding N, et al. The Global Distribution and Transmission Limits of Lymphatic Filariasis: Past and Present. Parasites & Vectors. 2014 Oct; 7: 466

• Croker C, Reporter R, Redelings M, et al. Strongyloidiasis-Related Deaths in the United States, 1991-2006. Am J Trop Med Hyg. 2010 Aug; 83(2): 422-426

• Gavignet B, Piarroux R, Aubin F, et al. Cutaneous Manifestations of Human Toxocariasis. Ja Am Acad Dermatol. 2008 Dec; 59(6): 1031-1042

• Grady BE, Baum B. A Classic Case of Cutaneous Larva Migrans. 2013. http://www.consultantlive.com/skin- diseases/content/article/10162/2148906

• Grayson W. Infectious Diseases of the Skin. In: McKee’s Pathology of the Skin 4th ed. Edinburgh: Elsevier/Saunders; 2012: 761-895

• Hoerauf A, Mand S, Volkmann L, et al. Doxycycline in the Treatment of Human Onchocerciasis: Kinetics of Wolbachia Endobacteria Reduction and of Inhibition of Embryogenesis in Female Onchocerca worms. Microbes Infect. 2003 Apr; 5(4): 261-73

• Housholder AL. Parasites and Other Creatures. In: Review of Dermatology. Toronto: Elsevier; 2017: 312-319

• James WD, Berger TG, Elston DM. Parasitic Infestations, Stings, and Bites. In: Andrews’ Diseases of the Skin: Clinical Dermatology 11th ed. Edinburgh: Elsevier/Saunders; 2011: 414-447

• Kollipara R, Peranteau AJ, Nawas ZY, et al. Emerging Infectious Diseases with Cutaneous Manifestations. J Am Acad Dermatol. 2016 Jul; 75(1): 19-31 REFERENCES

• Lupi O, Downing C, Lee M, et al. Mucocutaneous Manifestations of Helminth Infections. J Am Acad Dermatol. 2015 Dec; 73(6): 929-957

• Nelson SA, Warschaw KE. Protozoa and Worms. In: Dermatology 3rd ed. Edinburgh: Elsevier/Saunders; 2012: 1391-1421

• Puthiyakunnon S, Boddu S, Li Y, et al. Strongyloidiasis-An Insight into Its Global Prevalence and Management. PLoS Negl Trop Dis. 2014 Aug; 8(8): e3018

• Sanprasert V, Sujariyakul A, Nuchprayoon S. A Single Dose of Doxycycline in Combination with Diethylcarbamazine for Treatment of Bancroftian Filariasis. Southeast Asian J Trop Med Public Health. 2010 Jul; 41(4): 800-12

• Sorvillo, FJ, DeGiorgio C, Waterman SH. Deaths from Cysticercosis, United States. Emerg Infect Dis. 2007 Feb; 13(2): 230-235

• www.cdc.gov/parasites

• www.uptodate.com/contents/strongyloidiasis

• www.visualdx.com

• www.who.int/intestinal_worms/en QUESTIONS?